Drug delivery systems (DDS) are technologies for delivering drugs to target sites such as cells and tissues to enhance drug efficacy and reduce adverse effects by controlling drug absorption and release.
Drug delivery systems include transdermal delivery, which allows topical drug application, as well as conventional oral administration. Research has been continuously conducted to find ways to administer pharmaceutical compounds like drugs both efficiently and safely. Among them is an injection, which can be bothersome, cause pain depending on the type of patient, and has limitations for drug control besides temporary injection of drugs.
To overcome the disadvantages of an injection, research has been carried out on microstructures (microneedles), which are much smaller and cause less pain than conventional syringes. Studies are also being conducted in several areas of drug delivery, blood collection, biosensors and skin care.
Conventional microneedle production methods include U.S. Pat. No. 6,334,856 “Microneedle devices and methods of manufacture and use thereof” and Republic of Korea Patent No. 10-0793615 “Biodegradable solid microneedles and methods for preparing the same.”
The aforementioned patents relate to i) the manufacture of microneedles by injecting a biodegradable viscous material into a micro-mold made from thermosetting polymer, drying and removing it from the mold (molding process) and ii) the manufacture of microneedles through the steps of coating a biodegradable viscous material to form biodegradable solid microneedles, drawing the coated biodegradable viscous material with the frame which has been patterned as a pillar, drying and cutting the drawn biodegradable viscous material (drawing process).
However, the biodegradable polymer microstructures manufactured using those conventional methods present such problems as bending and deformation during skin penetration due to their relatively low mechanical strength.
In particular, when the derivatives of polymers with high elasticity are used as a raw material, it poses limitations for the production of microstructures using the molding or drawing process, such as the inability to obtain a desired uniform shape, as well as disadvantages such as difficulty achieving the required mechanical strength of the microstructure necessary for skin penetration.
As used in the present invention, hyaluronic acid is a biodegradable polymer composed of repeating disaccharide units consisting of N-acetyl glucosamine and gluconic acid.
Microstructures manufactured using hyaluronic acid are more easily formed with lower viscosity if the average molecular weight of hyaluronic acid is lower; the higher the molecular weight of the HA, the mechanical properties and viscosity of the microstructure become higher. Such characteristics lead to the use of hyaluronic acid with low molecular weight as a common material for microstructures, but microstructures manufactured using low-molecular hyaluronic acid are prone to breaking or bending during skin penetration.
In the present invention, the inventors developed crosslinked hyaluronic acid hydrogels and the method of manufacturing microstructures using such hydrogels as a primary material in order to manufacture microstructures that use low-molecular hyaluronic acid, provide the mechanical properties appropriate for skin penetration, and are suitable for drug delivery and skin care as they easily dissolve or swell in skin.